The overall goal of this research is to understand, on a molecular level, the mechanism of the Adenosylcobalamin (Ado-B12 or Coenzyme B12)-dependent rearrangement reactions. A focal point of the research will be key cobalt-C5' bond homolysis of Ado-B12 and the steric, electronic, axial 5,6-dimethylbenzimidazole base, radical cage, and other factors influencing this crucial step of the enzymatic reactions. The B12 coenzyme is essential for the normal maturation of erythrocytes and, in man, insufficient amounts of B12 causes Pernicious Anemia. B12 is an essential cofactor in man for methylmalonyl-CoA mutase, an enzyme which catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA. Recent work indicates that there exists a family of functionally related and probably mechanistically similar enzymes that utilize a diiron (Fe2) rather than a B12 (Co) cofactor, noteably leucine-2,3-amino-mutase and the ribonucleotide reductases. These enzymes are widely distributed in humans, mammals, and plants. It appears, therefore, that a molecular understanding of the free radical chemistry and mechanism of action of the Ado-B12 -dependent reactions has a broader significance than was previously thought.